Technologies
CpG-free DNA
The mammalian innate immune system has the ability to recognize and direct a response against incoming foreign DNA. The primary signal that triggers this response is unmethylated CpG motifs present in the DNA sequence of various disease-causing pathogens. These motifs are rare in vertebrate DNA, but abundant in bacterial and some viral DNAs. Because non-viral gene therapy involves the delivery of DNA from plasmids of bacterial origin, an acute inflammatory response of variable severity inevitably results.
Another major limitation of gene delivery vectors for gene therapy applications is the rapid decline of transgene expression in vivo. Promoter inactivation through CpG methylation is often the primary factor limiting long-lasting gene expression. The transcriptional activity of the widely used and CpG-rich CMV promoter, although robust is prone to inactivation within a few weeks.
To alleviate these limitations, InvivoGen Therapeutics has developed a new family of plasmids for non-viral gene therapy completely devoid of CpG dinucleotides. These pCpG plasmids are non immunostimulatory even at high doses and in contrast to CMV-based plasmids allow sustained expression.
Furthermore, pCpG plasmids yield high levels of transgene expression when injected through a hydrodynamic-based delivery technique. This technique is applicable to large organs in particular the liver, muscle, and kidneys. To improve the selectivity of transgene expression to a given organ, a new generation of pCpG plasmids is currently under contruction that feature CpG-free organ-specific promoters.
InvivoGen Therapeutics has a recently granted patent covering the technology of pCpG plasmids. A selection of pCpG plasmids is commercially available and can be obtained from InvivoGen.
Another major limitation of gene delivery vectors for gene therapy applications is the rapid decline of transgene expression in vivo. Promoter inactivation through CpG methylation is often the primary factor limiting long-lasting gene expression. The transcriptional activity of the widely used and CpG-rich CMV promoter, although robust is prone to inactivation within a few weeks.
To alleviate these limitations, InvivoGen Therapeutics has developed a new family of plasmids for non-viral gene therapy completely devoid of CpG dinucleotides. These pCpG plasmids are non immunostimulatory even at high doses and in contrast to CMV-based plasmids allow sustained expression.
Furthermore, pCpG plasmids yield high levels of transgene expression when injected through a hydrodynamic-based delivery technique. This technique is applicable to large organs in particular the liver, muscle, and kidneys. To improve the selectivity of transgene expression to a given organ, a new generation of pCpG plasmids is currently under contruction that feature CpG-free organ-specific promoters.
InvivoGen Therapeutics has a recently granted patent covering the technology of pCpG plasmids. A selection of pCpG plasmids is commercially available and can be obtained from InvivoGen.